Fig. 4.

Neuropathologic changes. A. Brain of long term surviving F98 glioma bearing rat that had received 20 μg of carboplatin by CED, followed by three 5 Gy fractions of X-rays, and was euthanized at 180 d. No residual tumor cells were identified. There was a light infiltrate of lymphocytes with scattered clumps of dystrophic calcific debris (400×). B. Brain of a non-tumor bearing rat that had received 40 μg of carboplatin (10 μL) by CED and was euthanized 3 weeks later. There was focal necrosis of white matter at the site of administration, an infiltrate of foamy macrophages and scattered lymphocytes (200×). C. Same animal as (B) but another area within the white matter that showed microscopic foci of hemorrhage and an infiltrate of foamy macrophages (200×). D. Brain of a non-tumor bearing rat that received 40 μg of carboplatin by CED followed by three 5 Gy fractions of X-rays and was euthanized 3 weeks later. There was white matter necrosis, scattered lymphocytes and macrophages, and calcified cellular debris (400×). Based on these observations a dose of 20 μg of carboplatin alone or in combination with X-irradiation was selected for therapy studies.